| neuroTranSmiTTerS | opinion
Cholinergic nerve cells have a specific high-affinity uptake system for choline; acetylcholine is synthesised in the cell cytoplasm and then retained in storage vesicles until needed. after it has elicited a response, acetylcholine released into the synaptic cleft is broken down by a membrane-bound enzyme called acetylcholinesterase. There are two types of acetylcholine
receptor, the so-called nicotinic and muscarinic receptors (named after their relative affinity for particular ligands). Those in the brain are mainly of the nicotinic type. They consist of five protein subunits arranged to form an ion channel across the cell membrane. acetylcholine elicits its physiological response by increasing the passage of ions through this channel. Cholinergic pathways are particularly
concentrated in specific regions of the brainstem and are involved mainly in cognitive functions, especially memory.
different messages. Some are excitatory, some are inhibitory, for example. it is the summation of all the messages reaching a particular cell that determines how that cell behaves, and how it then communicates with other nerve cells. These complex processes underlie all the information processing in the brain, from conscious thought to the regulation of blood pressure, from mood to the control of movement. over 50 different neurotransmitters
have been identified in the human brain. Their functioning is not static, but varies in response to a number of factors including various disease states and the age of the individual. The main neurotransmitters in the brain are acetylcholine; the catecholamines noradrenaline and dopamine; 5-hydroxy- typtamine (serotonin); excitatory amino acids such as glutamate; and inhibitory amino acids such as -aminobutyric acid (GaBa) and glycine. other known neurotransmitters include histamine, substance P, neurotensin and bradykinin.
Acetylcholine acetylcholine is formed from choline, an essential nutrient and one of the B-complex vitamins, by the action of the enzyme choline acetyltransferase.
Noradrenaline and dopamine noradrenaline and dopamine share a common precursor, the amino acid tyrosine. This is first hydroxylated to form an intermediate known as DoPa (or dihydroxyphenylalanine, to give it its full name). This then undergoes a decarboxylation step giving rise to dopamine, which then undergoes a further hydroxylation step to form noradrenaline (norepinephrine). Both dopamine and noradrenaline
function as neurotransmitters in the brain. Dopamine itself
is
especially abundant in a group of nerve cells known collectively as the basal ganglia, which are involved in the initiation and control of movement, while dopaminergic neurons are widely
distributed noradrenaline-containing neurons are
found in discrete areas of the brain such as the locus coeruleus, the pons and the reticular formation, which lie near the base of the brain and project to most other parts of the brain, particularly the cortex. These systems are involved in the control and maintenance of attention and arousal. Both dopamine and noradrenaline are
stored in presynaptic granules until needed. When they are released into the synapse, a small proportion is metabolised by specific enzymes, but the majority is taken up into the presynaptic nerve ending again and stored for further use.
Serotonin Serotonin is found throughout the body and, although only a very small proportion of the total amount occurs in the brain, it has some very important functions. it is formed by metabolism of the amino acid tryptophan via sequential hydroxylation and decarboxylation steps. These steps are also part of the synthetic route for melatonin (n-acetyl-5- methoxytryptamine), a hormone produced in the pineal gland that helps regulate the sleep-wake cycle. Like the catecholamines, serotonin is
The greatest concentration of
serotonin in the brain is found in the raphé
nuclei, which are located in the brain stem.
throughout the brain. Parkinson’s disease is associated with a decreased concentration of dopamine in the brain, while overactivity of dopaminergic pathways is thought to be involved in the aetiology of schizophrenia and paranoia. Dopaminergic pathways are also thought to be involved in certain types of behaviour, such as addictive behaviour (nicotine addiction, for example) and the type of behaviour exhibited by patients with attention deficit hyperactivity disorder (aDHD).
stored in presynaptic vesicles until released by a nerve impulse. once it has entered the synaptic cleft it reacts with postsynaptic serotonin receptors, of which there are several known subtypes, and is then taken up again into the presynaptic storage sites, with a small proportion being metabolised. The greatest concentration
of serotonin in the brain is found in the raphé nuclei, which are located in the brain stem, from where serotonergic neurons radiate throughout the brain. as this statement suggests, serotonergic path- ways are involved in a great
many brain functions, including the control of mood, regulation of sleep (tryptophan has been used as a dietary supplement to promote sleep), blood pressure, body temperature and pain perception. The formation of serotonin is sensitive to the amount of tryptophan in the diet, which may therefore affect these functions. in addition, the serotonin system is targeted by a number of classes of drug, including drugs used to treat depression, migraine, psychosis and
prime-journal.com | March 2011 ❚ 59
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